Cieśla et al. (2021) uncover intricate circuits of post-transcriptional regulation induced by the Myc oncogene, including alternative splicing and translational control, which are relevant for breast cancer prognosis and contribute to metabolic reprogramming and stem cell-like features of cancer cells.In this issue of Molecular Cell, Kaiho-Soma et al. (2021) demonstrate that the HECT-type E3 ubiquitin ligase TRIP12 cooperates with CRL complexes to promote PROTAC-induced degradation of neo-substrates by generating K29/K48-branched ubiquitin chains.We talk to the authors of "Structural basis for conformational equilibrium of the catalytic spliceosome" about their paper, advances in cryo-EM that made it possible, and the influence of their late mentor Kiyoshi Nagai, to whom the paper is dedicated.As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this piece, they discuss ways to make science more inclusive-from key points they wish their colleagues understood to actions those in the scientific community can take. These are the personal opinions of the authors and may not reflect the views of their institutions.Protein modifications modulate nearly every aspect of cell biology in organisms, ranging from Archaea to Eukaryotes. The earliest evidence of covalent protein modifications was found in the early 20th century by studying the amino acid composition of proteins by chemical hydrolysis. These discoveries challenged what defined a canonical amino acid. The advent and rapid adoption of mass-spectrometry-based proteomics in the latter part of the 20th century enabled a veritable explosion in the number of known protein modifications, with more than 500 discrete modifications counted today. Now, new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress in discovering new protein modifications and determining their function. In this review, we take an opportunity to revisit the historical discovery of key post-translational modifications, quantify the current landscape of covalent protein adducts, and assess the role that new computational tools will play in the future of this field.The retina dissects the visual scene into parallel information channels, which extract specific visual features through nonlinear processing. The first nonlinear stage is typically considered to occur at the output of bipolar cells, resulting from nonlinear transmitter release from synaptic terminals. In contrast, we show here that bipolar cells themselves can act as nonlinear processing elements at the level of their somatic membrane potential. Intracellular recordings from bipolar cells in the salamander retina revealed frequent nonlinear integration of visual signals within bipolar cell receptive field centers, affecting the encoding of artificial and natural stimuli. These nonlinearities provide sensitivity to spatial structure below the scale of bipolar cell receptive fields in both bipolar and downstream ganglion cells and appear to arise at the excitatory input into bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought that is, at the input stage of bipolar cells.Over the past 20 years, the use of telemedicine has increased exponentially. Its fundamental aim is to improve access to care. In this review, we assess the extent to which telemedicine has fulfilled this promise across medical domains. Additionally, we assess whether telemedicine has improved related health outcomes. Finally, we determine who has benefited from this novel form of health care delivery. A review of the literature indicates that (a) telemedicine has improved access to care for a wide range of clinical conditions ranging from stroke to pregnancy; (b) telemedicine in select circumstances has demonstrated improved health outcomes; and (c) telemedicine has addressed geographical, but less so social, barriers to care. For telemedicine to fulfill its promise, additional evidence needs to be gathered on health outcomes and cost savings, the digital divide needs to be bridged, and policy changes that support telemedicine reimbursement need to be enacted.The human microbiome contributes metabolic functions, protects against pathogens, educates the immune system, and through these basic functions, directly or indirectly, affects most of our physiologic functions. Here, we consider the human microbiome and its relationship to several major noncommunicable human conditions, including orodigestive tract cancers, neurologic diseases, diabetes, and obesity. We also highlight the scope of contextual macroenvironmental factors (toxicological and chemical environment, built environment, and socioeconomic environment) and individual microenvironmental factors (smoking, alcohol, and diet) that may push the microbiota toward less healthy or more healthy conditions, influencing the development of these diseases. Last, we highlight current uncertainties and challenges in the study of environmental influences on the human microbiome and implications for understanding noncommunicable disease, suggesting a research agenda to strengthen the scientific evidence base.An often-stated public health comment is that "vaccination is a victim of its own success." While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified "the reluctance or refusal to vaccinate despite availability of vaccines" as one of the 10 threats to global health in 2019. https://www.selleckchem.com/products/mtx-211.html The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.Introduction The goal for pediatric short bowel syndrome (SBS) patients is intestinal adaptation. Until recently, the medical management of pediatric SBS has centered on the prevention and treatment of complications in order to allow time for adaptation. Teduglutide, glucagon-like peptide 2 (GLP-2) analog, has recently been approved for use in pediatric SBS patients greater than 1 year of age as a novel agent to augment intestinal adaptation. Areas covered This article reviews the pharmacology, safety, efficacy, and tolerability of GLP-2 analog teduglutide in pediatric patients greater than 1 year of age. We review all current studies and discuss teduglutide's place in pediatric SBS therapy. Expert opinion Teduglutide marks the first successful pharmacological intervention that augments the natural process of adaptation safely and effectively in SBS pediatric patients. More studies and further development are needed to optimize its potential in other pediatric patients.